Alpha Lipoic Acid (ALA) Alleviates Hepatocytes Toxicity of Titanium Dioxide Nanoparticles in Rats

Aiman Al-Maathadi, Fardous Karawya, Said Al-Dalaen, Ahmed Aljabali, Anas Satari

Abstract


BACKGROUND: Titanium dioxide nanoparticles (TiO2 NPs) uptake may primarily cause adverse effects by inducing oxidative stress, resulting in cell damage, genotoxicity, inflammation, and immune response. To date, there are limited studies investigating the adverse effect of TiO2 NPs on liver health and no studies found a naturally occurring compound able to ameliorate such effect. Thus, this study investigated alpha lipoic acid (ALA) potential for reversing the biochemical and histopathological changes that TiO2 NPs exposure causes in rat liver.

METHODS: Thirty adult male albino rats were divided into: control rats received distilled water, control rats treated with 50 mg/kg ALA, rats intoxicated with TiO2 NPs, and TiO2 NPs-intoxicated rats treated 50 mg/kg ALA. Rats were sacrificed before blood samples were collected to assess the liver function using parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, albumin and total protein. Liver tissue homogenates were prepared to assess hepatic antioxidant and oxidative stress using parameters of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA). Liver tissue sections were used for histopathological analysis and caspase-3 immunohistochemical analysis.

RESULTS: TiO2 NPs produced deleterious effects on rat liver tissue, as confirmed through biochemical results, caspase-3 immunohistochemistry, and histological alterations. TiO2 NPs intoxication induced hepatocyte vacuolation, blood vessels congestion, biliary proliferation, apoptosis, and fibrosis. However, ALA treatment of TiO2 NPs-intoxicated rats significantly alleviated deleterious impact on the liver.

CONCLUSION: Administration of 600 mg/kg TiO2 NPs to rats resulted in hepatic degenerative lesions, depletion of GSH, oxidative stress, and apoptosis. However, these changes were mitigated by ALA administration. Therefore, ALA offers protection against deleterious effects of TiO2 NPs intoxication.

KEYWORDS: titanium dioxide nanoparticles, TiO2 NPs, hepatotoxicity, alpha-lipoic acid (ALA), rat


Full Text:

PDF

References


Jia X, Wang S, Zhou L, Sun L. The potential liver, brain, and embryo toxicity of titanium dioxide nanoparticles on mice. Nanoscale Res Lett. 2017; 12: 478, CrossRef.

Medina-Reyes EI, Delgado-Buenrostro NL, Díaz-Urbina D, Rodríguez-Ibarra C, Déciga-Alcaraz A, González MI, et al. Food-grade titanium dioxide (E171) induces anxiety, adenomas in colon and goblet cells hyperplasia in a regular diet model and microvesicular steatosis in a high fat diet model. Food Chem Toxicol. 2020; 146: 111786, CrossRef.

El-Sayed EM, Mansour AM, El-Sawy WS. Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol. 2017; 31(9): 21940, CrossRef.

Yaqub F, Latief N, Butt H, Naseer N, Riazuddin S. Alpha lipoic acid priming enhances the hepatoprotective effect of adipose derived stem cells in CCl4 induced hepatic injury in-vitro. Eur J Pharmacol. 2021; 906: 174201, CrossRef.

Ismawati I, Asni E, Mukhyarjon M, Romus I. Alpha lipoic acid inhibits expression of intercellular adhesion molecule-1 (ICAM-1) in type 2 diabetic mellitus rat models. Indones Biomed J. 2020; 12(1): 40-4, CrossRef.

Li CJ, Lv L, Li H, Yu DM. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol. 2012; 11: 73, CrossRef.

Qinna NA, Ghanim BY. Chemical induction of hepatic apoptosis in rodents. J Appl Toxicol. 2019; 39(2): 178-90, CrossRef.

Pradhan S, Roy S, Mandal S, Samanta A, Patra A, Das K, et al. Alpha-lipoic acid a cholesterol reducer for targeting acetaminophen induced uremic male albino rat models. Int J Pharm Sci Rev Res. 2014; 29(1): 62-6, article.

Kreyling WG, Holzwarth U, Schleh C, Kozempel J, Wenk A, Haberl N, et al. Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2. Nanotoxicology. 2017; 11(4): 443-53, CrossRef.

Aziz J, Aidaros AEE, Sabry MA, Ali A. Ameliorating effect of alpha-lipoic acid on methotrexate-induced histological and biochemical changes in the lung of adult albino rat. Egypt J Histol. 2020; 43(3): 878-90, CrossRef.

Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. Amsterdam: Elsevier Health Sciences; 2008, NLMID.

Tolunay O, Çelik T, Kömür M, Gezgin AE, Kaya MS, Çelik Ü. A rare cause of status epilepticus; alpha lipoic acid intoxication, case report and review of the literature. Eur J Paediatr Neurol. 2015; 19(6): 730-2, CrossRef.

Khadrawy SM, Mohamed HM, Mahmoud AM. Mesenchymal stem cells ameliorate oxidative stress, inflammation, and hepatic fibrosis via Nrf2/HO-1 signaling pathway in rats. Environ Sci Pollut Res. 2021; 28(2): 2019-30, CrossRef.

El-Maadawy W, Hammam O, Seif El-Din S, El-Lakkany N. α-Lipoic acid modulates liver fibrosis: a cross talk between TGF-β1, autophagy, and apoptosis. Hum Exp Toxicol. 2020; 39(4): 440-50, CrossRef.

Bashiri T, Ghorbanian MT, Zavareh S. Influence of alpha-lipoic acid on survival and proliferation of mesenchymal stem cells. J Kashan Univ Med Sci. 2016; 20(2): 133-40, article.

Liem S, Rostinawati T, Lesmana R, Sumiwi SA, Milanda T, Mutakin M, et al. Modulation of caspase-3 expression by Arcangelisia flava post acetaminophen-induced hepatotoxicity in rat’s liver. Indones Biomed J. 2018; 10(2): 148-55, CrossRef.

Dasiman R, Abd Malek M, Bahari EA, Zakaria FN, Hashim NK, Samsuddin A, et al. Effect of Croton caudatus Geiseler aqueous root extract on reproductive and biochemical parameters in male wistar rats. Indones Biomed J. 2020; 12(3): 251-60, CrossRef.

Korkmaz A, Ahbab MA, Kolankaya D, Barlas N. Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food Chem Toxicol. 2010; 48(10): 2865-71, CrossRef.

El-behairy DSA, Eldin NHD, Elbadry EE, Mohamed AA, Farrag IM. Hepato-renal toxicity of titanium dioxide nanoparticles and the protective effects of Moringa oleifera leaves extract and vitamin E in male albino rats. Egypt J Hosp Med. 2019; 75(2): 2261-71, CrossRef.

Alarifi S, Ali D, Al-Doaiss AA, Ali BA, Ahmed M, Al-Khedhairy AA. Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats. Int J Nanomedicine. 2013; 8: 3937-43, CrossRef.

Abdulrazzaq AM, Badr M, Gammoh O, Abu Khalil AA, Ghanim BY, Alhussainy TM, et al. Hepatoprotective actions of ascorbic acid, alpha lipoic acid and silymarin or their combination against acetaminophen-induced hepatotoxicity in rats. Medicina (Kaunas). 2019; 55(5): 181, CrossRef.

Pari L, Murugavel P. Protective effect of alpha-lipoic acid against chloroquine-induced hepatotoxicity in rats. J Appl Toxicol. 2004; 24(1): 21-6, CrossRef.

Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018; 54(4): 287-93, CrossRef.

Rizk MZ, Ali SA, Hamed MA, El-Rigal NS, Aly HF, Salah HH. Toxicity of titanium dioxide nanoparticles: effect of dose and time on biochemical disturbance, oxidative stress and genotoxicity in mice. Biomed Pharmacother. 2017; 90: 466-72, CrossRef.

Lammel T, Mackevica A, Johansson BR, Sturve J. Endocytosis, intracellular fate, accumulation, and agglomeration of titanium dioxide (TiO2) nanoparticles in the rainbow trout liver cell line RTL-W1. Environ Sci Pollut Res. 2019; 26(15): 15354-72, CrossRef.

Biola-Clier M, Gaillard J-C, Rabilloud T, Armengaud J, Carriere M. Titanium dioxide nanoparticles alter the cellular phosphoproteome in A549 cells. Nanomaterials. 2020; 10(2): 185, CrossRef.

Iversen TG, Skotland T, Sandvig K. Endocytosis and intracellular transport of nanoparticles: Present knowledge and need for future studies. Nano Today. 2011; 6(2): 176-85, CrossRef.

Hou J, Wang L, Wang C, Zhang S, Liu H, Li S, et al. Toxicity and mechanisms of action of titanium dioxide nanoparticles in living organisms. Journal of environmental sciences. 2019; 75: 40-53, CrossRef.

Zhu Y, Eaton JW, Li C. Titanium dioxide (TiO2) nanoparticles preferentially induce cell death in transformed cells in a Bak/Bax-independent fashion. PLoS One. 2012; 7(11): e50607, CrossRef.

Krüger K, Schrader K, Klempt M. Cellular response to titanium dioxide nanoparticles in intestinal epithelial Caco-2 cells is dependent on endocytosis-associated structures and mediated by EGFR. Nanomaterials. 2017; 7(4): 79, CrossRef.

Lammel T, Sturve J. Assessment of titanium dioxide nanoparticle toxicity in the rainbow trout (Onchorynchus mykiss) liver and gill cell lines RTL-W1 and RTgill-W1 under particular consideration of nanoparticle stability and interference with fluorometric assays. NanoImpact. 2018; 11: 1-19, CrossRef.

Pınar N, Çakırca G, Özgür T, Kaplan M. The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats. Biomed Pharmacother. 2018; 97: 1486-92, CrossRef.

Armagan I, Bayram D, Candan IA, Yigit A, Celik E, Armagan HH, et al. Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environ Toxicol Pharmacol. 2015; 39(3): 1122-31, CrossRef.




DOI: https://doi.org/10.18585/inabj.v15i3.2352

Copyright (c) 2023 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

Indexed by:

                  

               

                   

 

 

The Prodia Education and Research Institute